Toxicogenomics of Five Cytostatics in Fathead Minnow (Pimephales promelas) Larvae.

In this study, the toxicogenomic effects of five cytostatics (tamoxifen, methotrexate, capecitabine, cyclophosphamide, and ifosfamide) on fathead minnow (Pimephales promelas) larvae were evaluated. Post-fertilization eggs were exposed to increasing concentrations of the drugs for six days. The expression levels of two genetic biomarkers for toxicity and four thyroid hormone-related gene pathways were measured. Interestingly, the results showed that all concentrations of the five cytostatics affect the transcription levels of both toxicity biomarker genes. Additionally, the thyroid hormone-related genes had different expression levels than the control, with the most significant changes observed in those larvae exposed to cyclophosphamide and ifosfamide. While a previous study found no effects on fish morphology, this study suggests that the five cytostatics modify subtle molecular responses of P. promelas, highlighting the importance of assessing multibiological level endpoints throughout the lifecycle of animals to understand the full portrait of potential effects of cytostatics and other contaminants.

Molecular phylogeny and revision of species groups of Nearctic bombardier beetles (Carabidae, Brachininae, Brachinus ( Neobrachinus)).

Bombardier beetles of the genus Brachinus Weber are notorious for their explosive defensive chemistry. Despite ongoing research on their defense mechanism, life history, and ecology, the group lacks a robust molecular-based phylogeny. In this study, three loci from mitochondrial and nuclear genomes (COI, CAD, 28S) are used to reconstruct the phylogeny of the large subgenus Neobrachinus, and test species group boundaries hypothesized by Erwin (1970) based on morphological characters. Erwin's fumans species group is found to be polyphyletic, and is herein re-defined with eight new species groups erected to reflect clades based on molecular evidence: the cinctipennis, cyanipennis, galactoderus, gebhardis, mexicanus, phaeocerus, quadripennis, and tenuicollis species groups. Erwin's cordicollis group is also expanded to include Brachinus (Neobrachinus) medius and the americanus group.

Embryotoxicity of Five Cytostatics in Fathead Minnow (Pimephales promelas) Larvae.

Cytostatics are compounds used in chemotherapy, known to be genotoxic, mutagenic, and teratogenic at low concentrations. The amount of cytostatic drugs prescribed increases every year as does their release into the aquatic ecosystems, which possibly is a major concern for the health of aquatic organisms. This study aimed to evaluate the putative toxicity of five cytostatics to fathead minnow (Pimephales promelas) larvae: tamoxifen, capecitabine, methotrexate, cyclophosphamide, and ifosfamide. Eggs collected post-fertilization were exposed for 6 days to a range of concentrations, including one above environmental level. At all environmental concentrations, no significant difference in mortality, hatching time, length, heart rate, and presence of malformations were found. Altogether, these cytostatics do not seem embryotoxic to fish. Although, an increased proportion of complete swim bladder were found after ifosfamide's exposure, suggesting an interaction with the thyroid axis, involved in swim bladder development. Complementary work should address other endpoints, such as behavioral changes, reproductive success, and transgenerational effects.

Haemodiafiltration at increased plasma ionic strength for improved protein-bound toxin removal.

AIM: Protein-bound uraemic toxin accumulation causes uraemia-associated cardiovascular morbidity. Enhancing the plasma ionic strength releases toxins from protein binding and makes them available for removal during dialysis. This concept was implemented through high sodium concentrations ([Na+ ]) in the substituate of pre-dilution haemodiafiltration at increased plasma ionic strength (HDF-IPIS). METHODS: Ex vivo HDF-IPIS with blood tested increasing [Na+ ] to demonstrate efficacy and haemocompatibility. Haemocompatibility was further assessed in sheep using two different HDF-IPIS set-ups and [Na+ ] between 350 and 600 mmol L-1 . Safety and efficacy of para-cresyl sulphate (pCS) and indoxyl sulphate (IS) removal was further investigated in a randomized clinical pilot trial comparing HDF-IPIS to HD and HDF. RESULTS: Compared to [Na+ ] of 150 mmol L-1 , ex vivo HDF-IPIS at 500 mmol L-1 demonstrated up to 50% higher IS removal. Haemolysis in sheep was low even at [Na+ ] of 600 mmol L-1 (free Hb 0.016 ± 0.001 g dL-1 ). In patients, compared to HD, a [Na+ ] of 240 mmol L-1 in HDF-IPIS resulted in 40% greater reduction (48.7 ± 23.6 vs. 67.8 ± 7.9%; P = 0.013) in free IS. Compared to HD and HDF (23.0 ± 14.8 and 25.4 ± 10.5 mL min-1 ), the dialytic clearance of free IS was 31.6 ± 12.8 mL min-1 (P = 0.017) in HDF-IPIS, but [Na+ ] in arterial blood increased from 132 ± 2 to 136 ± 3 mmol L-1 (0 vs. 240 min; P < 0.001). CONCLUSION: HDF-IPIS is technically and clinically feasible. More effective HDF-IPIS requires higher temporary plasma [Na+ ], but dialysate [Na+ ] has to be appropriately adapted to avoid sodium accumulation.

Prolonged cholestasis triggered by hepatitis A virus infection and variants of the hepatocanalicular phospholipid and bile salt transporters.

Hepatitis A virus (HAV) infection resolves in most patients uneventfully within weeks from the onset of the disease. In rare cases, however, it may relapse or cause prolonged cholestasis. Here we present a case of a 36-year-old female patient who developed severe pruritus and jaundice three weeks after initially uncomplicated hepatitis A. A relapse of the infection was excluded. Since therapy with colestyramin, antihistaminics, naloxon and ursodeoxycholic acid (UDCA) did not improve symptoms, we decided to perform plasma absorption and to start rifampicin therapy. Under these measures, pruritus and jaundice, as well as serum bilirubin levels improved gradually and after four plasmapheresis sessions we were able to discharge the patient. Genetic testing showed the presence of two procholestatic polymorphisms, the c.3084 [GG] variant within the gene encoding the hepatocanalicular bile salt transporter ABCB11 and the c.711 [AT] variant of the phosphatidylcholine floppase ABCB4. We speculate that this compound ABCB4-ABCB11 genotype led to a severe intrahepatic cholestasis in the setting of HAV infection. In conclusion, our case suggests that polymorphisms within the hepatocanalicular transporters may contribute to a more pronounced course of HAV infection. Although dedicated studies in large cohorts of patients are needed to confirm this observation, we speculate that patients carrying procholestatic hepatobiliary transporter variants may benefit from vaccination against hepatitis A.

Ethmoid metastasis of endometrial carcinoma causing mucocoele of maxillary antrum.

We report a case of an antral mucocoele secondary to the obstruction of its ostium by metastatic endometrial carcinoma. This is the first report of such a cause for a mucocoele, and for a metastasis from such a tumour in the head and neck.

The Little Girl Who Wouldn't Walk : Exploring the Narratives of Preschoolers Through Previewing.

In the psychotherapy of preschoolers, the children's narratives-in which fantasy, symbol, and metaphor are used to represent internal states and perceptions-warrant special evaluation to clarify diagnosis and implement treatment. Previewing, a developmental phenomenon of the caregiver-infant interaction, may be of benefit in the psychotherapy of preschoolers. Previewing promotes children's predictive abilities in fantasy play, sensory perception, and script formation, enabling the therapist to see the world from the child's developmental perspective and assess the child's emotional functioning without evoking pathological defenses. Moreover, previewing techniques aid in the process of conflict resolution.

Working through conflict with self-destructive preschool children.

This case history charts the treatment of a preschooler who first presented at the age of three years and ten months with aggressive and self-destructive behaviors. During the initial months of treatment, the therapist focused upon establishing a therapeutic alliance with the child in order to evoke a transference reaction. Compelling evidence of the transference in this case occurred in the ninth month of treatment when the therapist told the child that she would be going on vacation. The child, whose own mother had abandoned him several times, responded with uncharacteristic physical and verbal abuse. Although the child engaged in aggressive and self-destructive play enactments almost from the onset of treatment, these behaviors intensified from the fifth month of treatment onwards, as it became evident that he had entered the working-through phase. Aggressive impulses were shown in his manipulation of toys and other objects, and self-destructive episodes emerged in the child's incessant efforts to jump from chairs and tables, as well as in repeated threats to "shoot" himself with a toy gun. The therapist was sensitive to the child's need to continually repeat and gradually modify these behaviors. She permitted their display without exhibiting shock or alarm, but at the same time, expressed concern for the child's safety and reinforced this concern by setting limits on his unacceptable behavior. Gradually, the child's self-destructive and aggressive tendencies abated. Further evidence that the conflict had been worked through was also seen in the child's ability to express a more realistic assessment of his home environment, one which reconciled the conflict between "good" and "bad" impulses. This advancement in perception was demonstrated by the child's verbal recognition that while his mother was capable of doing "bad" things, she was still his mother and he loved her. Prior to the termination of treatment, both the child's grandmother and teachers reported significant improvement in the child's behavior and linguistic abilities.